期刊
CIRCULATION RESEARCH
卷 131, 期 6, 页码 545-554出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/CIRCRESAHA.122.320796
关键词
blood pressure; carotid-femoral pulse wave velocity; hemodynamics; human genetics; vascular stiffness
资金
- National Institutes of Health (NIH) [K23HL133843, R01-HL153646, R01-HL157108, R01-AG074989, U01HL160277, U01-TR003734, R01-DK123104, U24-DK060990]
- American Heart Association Bugher Award
- NIH [R01-HL153646, U01-TR003734, R01-HL121510, U01-TR003734-01S1, UO1-HL-160277, R33-HL-146390, K24-AG070459, R01-AG058969, R01-HL104106, P01-HL094307, R03-HL146874, R56-HL136730, R01 HL155599, R01HL157264, R01HL155, 1R01HL153646]
- National Heart, Lung and Blood Institute [NO1HC-25195, HHSN268201500001I, 75N92019D00031]
- Evans Medical Foundation
- Department of Medicine, Boston University School of Medicine
- British Heart Foundation Centre of Research Excellence [RE/18/4/34215]
- National Institute for Health Research Clinical Lectureship at St. George's, University of London [CL-2020-16-001]
- United Kingdom Research and Innovation Medical Research Council [MC_ UU_00002/7]
- National Institute for Health Research Cambridge Biomedical Research [BRC-1215-20014]
- [HL076784]
- [AG028321]
- [HL070100]
- [HL060040]
- [HL080124]
- [HL071039]
- [HL077447]
- [HL107385 R01HL142983]
- [R01HL126136]
- [R01 HL 080124]
In this study, we used prospective cohort data and Mendelian randomization analyses to show that greater large artery stiffness (LAS) is associated with an increased risk of developing type 2 diabetes. LAS may play an important role in glucose homeostasis and could serve as a useful marker for future diabetes risk.
Background: Microvascular damage from large artery stiffness (LAS) in pancreatic, hepatic, and skeletal muscles may affect glucose homeostasis. Our goal was to evaluate the association between LAS and the risk of type 2 diabetes using prospectively collected, carefully phenotyped measurements of LAS as well as Mendelian randomization analyses. Methods: Carotid-femoral pulse wave velocity (CF-PWV) and brachial and central pulse pressure were measured in 5676 participants of the FHS (Framingham Heart Study) without diabetes. We used Cox proportional hazards regression to evaluate the association of CF-PWV and pulse pressure with incident diabetes. We subsequently performed 2-sample Mendelian randomization analyses evaluating the associations of genetically predicted brachial pulse pressure with type 2 diabetes in the UKBB (United Kingdom Biobank). Results: In FHS, individuals with higher CF-PWV were older, more often male, and had higher body mass index and mean arterial pressure compared to those with lower CF-PWV. After a median follow-up of 7 years, CF-PWV and central pulse pressure were associated with an increased risk of new-onset diabetes (per SD increase, multivariable-adjusted CF-PWV hazard ratio, 1.36 [95% CI, 1.03-1.76]; P=0.030; central pulse pressure multivariable-adjusted CF-PWV hazard ratio, 1.26 [95% CI, 1.08-1.48]; P=0.004). In United Kingdom Biobank, genetically predicted brachial pulse pressure was associated with type 2 diabetes, independent of mean arterial pressure (adjusted odds ratio, 1.16 [95% CI, 1.00-1.35]; P=0.049). Conclusions: Using prospective cohort data coupled with Mendelian randomization analyses, we found evidence supporting that greater LAS is associated with increased risk of developing diabetes. LAS may play an important role in glucose homeostasis and may serve as a useful marker of future diabetes risk.
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